Patent GB-779829-A (GB)
Title: Polyglycol ethers and their manufacture
IPC: C07C233/00
Filed: 1954-11-22
Abstract: The invention comprises polyglycol ethers of the formula: <FORM:0779829/IV(b)/1> in which n represents a whole number from 2 to 20, R represents hydrogen or a hydrocarbon radical containing at most 7 carbon atoms, and R1 and R11 each represent a hydrogen atom or an alkyl or alkoxy-alkyl group containing at most 4 carbon atoms provided that R1 and R11 represent hydrogen in at least n/2 of the residues <FORM:0779829/IV(b)/2> x represents hydrogen or a hydrocarbon radical containing at most 7 carbon atoms, "Aryl" represents an alkyl- or alkoxy-substituted phenyl residue and Y represents hydrogen, an aliphatic or cycloaliphatic hydrocarbon radical or the residue "Aryl".  Such compounds are obtained by reacting a reactive ester (e.g. a hydrohalic acid or an organic sulphonic acid ester) of a hydroxy-carboxylic acid arylide of the formula: <FORM:0779829/IV(b)/3> with a polyglycol, if desired in the form of a metal alcoholate, or in the presence of a metal alcoholate. The reaction may be formed in stages, such as by first forming a glycol ether of an aliphatic hydroxycarboxylic acid arylide and converting the product or its alcoholate into a polyglycol ether. Alternatively a reactive carboxyl derivative of a polyglycol ether of an aliphatic hydroxy carboxylic acid is reacted with the appropriate arylamine, suitably in the presence of an acid-binding agent. Mixtures of final products with n having different values may be formed.  The products have therapeutic properties.  In Example (1) the acid chloride obtained by treating the ether of pentaethylene glycol monomethyl ether with glycollic acid of the formula CH3(OCH2CH2)5OCH2COOH is reacted with N-n-butyl-2 : 6-dimethylaniline to form the ether of pentaethylene glycol monomethyl ether with glycollic acid N-n-2 : 6-N-dimethylphenylamide.  Similarly obtained are (2) the ether of octaethylene glycol monomethyl ether with glycollic acid-N-butyl-N-2 : 6-dimethylphenylamide; (3) a similar compound having 6 to 8 ethylenoxy groups; (4) the ether of diethylene glycol monomethyl ether with glycollic acid N-2 : 6-dimethylphenyl amide, and the corresponding compound with 6 to 8 ethylenoxy groups; (5) the ether of the polyethylene glycol monomethyl ether with a -hydroxycaproic acid of the formula: <FORM:0779829/IV(b)/4> in which n has the average value of about 6 to 8 ; (6) the ether of hepta-ethylene glycol monomethyl ether with glycollic acid N-p-ethoxyphenyl amide; (9) the ehters of penta- and hexaethylene glycol monomethyl ethers of glycollic acid N - 2:6 - dimethyl - 4 - n - butoxyphenylamide.  In Example (7) hepta-ethylene glycol monomethyl ether is reacted with sodium and the product with a -chloracetic acid-N-n-butylN:2:6-dimethylphenylamide to give the ether of hepta-ethylene glycol monomethyl ether with glycollic acid - N - n - butyl - N - 2:6 - dimethylphenylamide.  Analogously produced are similar tetra- and hexaethylene glycol derivatives and compounds with N-n-hexyl and n-heptyl substituents.  Similarly obtained are (10) the same product as in Example (1); (13) the ether of hexa-ethylene glycol monomethyl ether with glycollic acid-N:N-di-o-tolylamide.  In Example (8) a -chloracetic acid-N-n-butyl 2:6 - dimethyl - phenyl - amide is reacted with the sodium derivatives of di- and tri-ethylene glycol respectively to give the corresponding ethers.  In Example (11) the ether of 1:2-propylene glycol with glycollic acid N-butyl-N-2:6-dimethylphenylamide is heated in a sealed tube with ethylene oxide in the presence of sodium hydroxide to give a mixture of ethers of the formula: <FORM:0779829/IV(b)/5> where n has an average value of 7 which can be fractionated by countercurrent extraction between two liquid phases.  In Example (12) the sodium derivative of octa-ethylene glycol-o  - methyl ether - o 1 - [2 - hydroxy - 3 - ethoxypropyl ether-(1)] is reacted with a -chloracetic acid N-n-heptyl-2:6-dimethylphenylamide to give the corresponding ether.ALSO:Polyglycol ethers of the formula <FORM:0779829/VI/1> in which n represents a whole number from 2 to 20, R represents hydrogen or a hydrocarbon radical containing at most 7 carbon atoms and R1 and R11 each represent a hydrogen atom or an alkyl or alkoxy-alkyl group containing at most 4 carbon atoms, provided that R1 and R11 represent hydrogen in at least <FORM:0779829/VI/2> of the residues -(OCHR1 - CHR11)-, X represents hydrogen or a hydrocarbon radical containing at most 7 carbon atoms, "Aryl" represents an alkyl- or alkoxy-substituted phenyl residue and Y represents hydrogen, an aliphatic or cycloaliphatic hydrocarbon radical or the residue "Aryl" have pharmacoligical, especially local anaesthetic action and may be formed into pharmaceutical preparations with an organic or inorganic carrier for enteral, parenteral or oral application.  Specified carriers are water, gelatin, lactose, starch, magnesium stearate, talc, vegetable oils, benzyl alcohol, gums, polyalkylene gylcols, petroleum jelly, and cholesterol, or other therapeutically active substances, preservatives, stabilizing, wetting or emulsifying agents, salts which vary the osmotic pressure or buffer substances may be added.  The compositions may be formed into tablets, dragees, salves, creams, solutions, suspension or emulsions.  The preparation of the glycol ethers is described (see Group IV(b)).